Effect of des-Tyr1-[gamma]-endorphin and des-enkephalin-[gamma]-endorphin on active and passive avoidance behavior of rats; A dose-response relationship study

The potency of two β-endorphin fragments, des-Tyr1-γ-endorphin (DTγE, βE-(2–17)) and des-enkephalin-γ-endorphin (DEγE, βE-(6–17)) was compared on extinction of pole-jumping avoidance behavior and on retention of a one-trial step-through passive avoidance procedure. Both peptides facilitated the extinction of pole-jumping avoidance behavior and attenuated passive avoidance behavior. The γ-type endorphins exhibited an inverted U-shaped dose-response curve on passive avoidance behavior but not on extinction of pole-jumping avoidance behavior. DEγE appeared to be approximately three times more potent than DTγE on extinction of pole-jumping avoidance behavior but one hundred times more potent on passive avoidance behavior. It is suggested that DEγE rather than DTγE represents the endogenous neurolepticlike neuropeptide derived from β-endorphin

γ-endorphin and Nα-acetyl-γ-endorphin interfere with distinct dopaminergic systems in the nucleus accumbens via opioid and non-opioid mechanisms

Low doses (10 ng) of the dopamine agonist apomorphine induced hypolocomotion when injected into the nucleus accumbens of rats. This behavioral response was antagonized by local treatment with either the opioid peptide γ-endorphin (γE) or the non-opioid peptide Nα-acetyl-γ-endorphin (AcγE) in a dose of 100 pg. High doses of apomorphine (10 μg) or amphetamine (2 μg) injected into the nucleus accumbens resulted in hyperlocomotion. This response was blocked by pretreatment with γE but not with AcγE. This effect of γE could be prevented by local treatment with naloxone. Neither peptides interfered with the apomorphine-induced stereotyped sniffing when the substances were injected into the nucleus caudatus. It is concluded that γE and AcγE differentially interact with distinct dopaminergic systems in the nucleus accumbens of the rat brain via an opioid and a non-opioid mechanism, suggesting that the peptide fragments originating from pro-opiomelanocortin may be specifically implicated in the control of dopaminergic activity in this brain area

Arginine-vasopressin content of hippocampus and amygdala during passive avoidance behavior in rats

Arginine-vasopressin (AVP) is involved in memory processes. The memory effects of AVP are mediated by neuronal mechanisms taking place in limbic-midbrain structures. Therefore, immunoreactive AVP (IR-AVP) was measured in hippocampus and amygdala of male Wistar rats during acquisition and retention of passive avoidance behavior. IR-AVP concentration was decreased in the hippocampus immediately after the learning trial while IR-AVP content of the amygdala was not affected. Animals that showed the passive avoidance response (good avoiders) at the 24 h or 120 h retention test had a reduced IR-AVP concentration in the hippocampus immediately after the test. However, IR-AVP content of the hippocampus was not different from that of non-shocked control animals when measured immediately before the 120 h retention test. Poor avoiders that showed only minor avoidance behavior did not differ in hippocampal IR-AVP content from non-shocked control animals. IR-AVP content of the amygdala was also not altered after the retention session. These effects on IR-AVP content could only be shown in animals that were trained and habituated to the passive avoidance procedure. Such trained and habituated animals had an IR-AVP level in the hippocampus which did not differ from that of animals that were left undisturbed until sacrifice. When the animals were not trained, but place for the first time in the passive avoidance apparatus without being exposed to the learning trial, the hippocampal IR-AVP content was reduced. Under these circumstances additional exposure to the electric footshock did not lead to a measurable further decrease in IR-AVP content of the hippocampus. Again, IR-AVP content of the amygdala was not affected. It is proposed that learning and retention of a passive avoidance response is associated with a reduction in hippocampal IR-AVP content. The reduction ppossibly reflects increased secretory activity at the peptidergic terminal. This AVP released at the terminal might be instrumental in facilitating memory formation

Arginine-vasopressin content of hippocampus and amygdala during passive avoidance behavior in rats

Arginine-vasopressin (AVP) is involved in memory processes. The memory effects of AVP are mediated by neuronal mechanisms taking place in limbic-midbrain structures. Therefore, immunoreactive AVP (IR-AVP) was measured in hippocampus and amygdala of male Wistar rats during acquisition and retention of passive avoidance behavior. IR-AVP concentration was decreased in the hippocampus immediately after the learning trial while IR-AVP content of the amygdala was not affected. Animals that showed the passive avoidance response (good avoiders) at the 24 h or 120 h retention test had a reduced IR-AVP concentration in the hippocampus immediately after the test. However, IR-AVP content of the hippocampus was not different from that of non-shocked control animals when measured immediately before the 120 h retention test. Poor avoiders that showed only minor avoidance behavior did not differ in hippocampal IR-AVP content from non-shocked control animals. IR-AVP content of the amygdala was also not altered after the retention session. These effects on IR-AVP content could only be shown in animals that were trained and habituated to the passive avoidance procedure. Such trained and habituated animals had an IR-AVP level in the hippocampus which did not differ from that of animals that were left undisturbed until sacrifice. When the animals were not trained, but place for the first time in the passive avoidance apparatus without being exposed to the learning trial, the hippocampal IR-AVP content was reduced. Under these circumstances additional exposure to the electric footshock did not lead to a measurable further decrease in IR-AVP content of the hippocampus. Again, IR-AVP content of the amygdala was not affected. It is proposed that learning and retention of a passive avoidance response is associated with a reduction in hippocampal IR-AVP content. The reduction ppossibly reflects increased secretory activity at the peptidergic terminal. This AVP released at the terminal might be instrumental in facilitating memory formation

Levels of arginine-vasopressin in cerebrospinal fluid during passive avoidance behavior in rats

The concentration of immunoreactive arginine-vasopressin (IR-AVP) was measured in the cerebrospinal fluid (CSF) during acquisition and retention of passive avoidance behavior. IR-AVP level in CSF of male Wistar rats immediately after the learning trial was increased; the rate of which was related to the intensity of the electric footschock during the learning trial and the avoidance latency as measured 1 day after the learning trial. Immediately after the 24 h retention test IR-AVP levels were significantly increased in rats subjected to the low (0.25 mA) shock intensity during the learning trial, but IR-AVP levels of rats exposed to the high shock (1.0 mA) were under the limit of detection. If the retention test was postponed till 5 days after the learning trial, the increase of IR-AVP level in the CSF was related to avoidance latencies which reflect the intensity of aversive stimulation (electric footshock). The results suggest an association between central AVP release and passive avoidance behavior and may be indicative of the role of this peptide in neuronal mechanisms underlying learning and memory processes

N[alpha]-acetyl-[gamma]-endorphin is an endogenous non-opioid neuropeptide with biological activity

Nα-acetyl-γ-endorphin (AcγE) was identified in the rat neurointermediate pituitary, based on its immunological properties, comigration with synthetic AcγE on HPLC and resistance to aminopeptidase-M degradation. The peptide appeared to be the main form of γ-endophin (γE) in this tissue and in brain areas remote from the hypothalamus (hippocampus, septum, amygdala). The anterior pituitary, the hypothalamus and the thalamus contained almost exclusively the non-acetylated form of γE. In contrast to γE, AcγE was completely devoid of specific affinity for brain opiate binding sites. Yet, the peptide mimicked γE in that if potently attenuated passive avoidance behaviour in rats, when injected topically into the nucleus accumbens. It is concluded that AcγE is an endogenous neuropeptide with non-opioid biological activity. Nα-acetylation may not merely represent a mechanism for the inactivation of opioid activities of endorphins, but rather allow the organism to select specific sets of biological activities that reside in the endorphin structure